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Open AccessJournal ArticleDOI

Mammalian Base Excision Repair: the Forgotten Archangel

Grigory L. Dianov, +1 more
- 01 Apr 2013 - 
- Vol. 41, Iss: 6, pp 3483-3490
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TLDR
This review is to critically examine controversial and newly emerging questions about mammalian BER pathways, mechanisms regulating BER capacity, BER responses to DNA damage and their links to checkpoint control of DNA replication.
Abstract
Base excision repair (BER) is a frontline repair system that is responsible for maintaining genome integrity and thus preventing premature aging, cancer and many other human diseases by repairing thousands of DNA lesions and strand breaks continuously caused by endogenous and exogenous mutagens. This fundamental and essential function of BER not only necessitates tight control of the continuous availability of basic components for fast and accurate repair, but also requires temporal and spatial coordination of BER and cell cycle progression to prevent replication of damaged DNA. The major goal of this review is to critically examine controversial and newly emerging questions about mammalian BER pathways, mechanisms regulating BER capacity, BER responses to DNA damage and their links to checkpoint control of DNA replication.

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Citations
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Journal ArticleDOI

Development and applications of CRISPR-Cas9 for genome engineering.

TL;DR: In this paper, the authors describe the development and applications of Cas9 for a variety of research or translational applications while highlighting challenges as well as future directions, and highlight challenges and future directions.

Development and Applications of CRISPR-Cas9 for Genome Engineering

TL;DR: The development and applications of Cas9 are described for a variety of research or translational applications while highlighting challenges as well as future directions.
Journal ArticleDOI

Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity

TL;DR: In this paper, an approach that combines a Cas9 nickase mutant with paired guide RNAs to introduce targeted double-strand breaks is described. But the approach is limited to mouse zygotes.

Double Nicking by RNA-Guided CRISPR Cas9 for Enhanced Genome Editing Specificity

TL;DR: It is demonstrated that using paired nicking can reduce off-target activity by 50- to 1,500-fold in cell lines and to facilitate gene knockout in mouse zygotes without sacrificing on-target cleavage efficiency.
Journal ArticleDOI

Mechanisms of DNA damage, repair, and mutagenesis.

TL;DR: This introductory review will delineate mechanisms of DNA damage and the counteracting repair/tolerance pathways to provide insights into the molecular basis of genotoxicity in cells that lays the foundation for subsequent articles in this issue.
References
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TL;DR: The spontaneous decay of DNA is likely to be a major factor in mutagenesis, carcinogenesis and ageing, and also sets limits for the recovery of DNA fragments from fossils.
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TL;DR: It is shown that in clinical specimens from different stages of human tumours of the urinary bladder, breast, lung and colon, the early precursor lesions commonly express markers of an activated DNA damage response.
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TL;DR: The aesthetic appeal of the DNA double helix initially hindered notions of DNA mutation and repair, which would necessarily interfere with its pristine state, but it has since been recognized that DNA is subject to continuous damage and the cell has an arsenal of ways of responding to such injury.
Journal ArticleDOI

Role of poly(ADP-ribose) formation in DNA repair

TL;DR: The results indicate that unmodified polymerase molecules bind tightly to DNA strand breaks; auto-poly(ADP-ribosyl)ation of the protein then effects its release and allows access to lesions for DNA repair enzymes.
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